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Neural circuit for the sleep-wake regulation by prostaglandins D_2 and E_2

Research Project

Project/Area Number 04404026
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field General medical chemistry
Research InstitutionOsaka Bioscience Institute

Principal Investigator

HAYAISHI Osamu  Osaka Bioscience Institute Director, 所長 (40025507)

Co-Investigator(Kenkyū-buntansha) OSAKA Toshimasa  Osaka Bioscience Institute Department of Molecular Behavioral Biology Researcher, 第2研究九部, 研究員 (30152101)
WATANABE Kikuko  Osaka Bioscience Institute Department of Molecular Behavioral Biology Researcher, 第2研究部, 研究員 (90211672)
MATSUMURA Hitoshi  Osaka Bioscience Institute Department of Molecular Behavioral Biology Vice-Head, 第2研究部, 研究副部長 (50173886)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥28,000,000 (Direct Cost: ¥28,000,000)
Fiscal Year 1994: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1993: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1992: ¥20,000,000 (Direct Cost: ¥20,000,000)
KeywordsProstaglandin D_2 / Prstaglandin E_2 / Sleep / Wakefulness / Prostaglandin D synthase / Subarachnoid space / beta-Trace / Cerebrospinal fluid / プロスタグランジン / ニューロン / 軟膜 / マイクロダイアリシス / 脈絡叢 / 神経回路網 / 視束前野 / セロトニン
Research Abstract

We previously hypothesized that prostaglandin (PG) D_2 and PGE_2 are endogenous sleep-wake regulating substances. In this study, we examined the site of action of the sleep-promoting effect of PGD_2 with more than 200 rats and found that continuous and bilateral infusion of PGD_2 into the subarachnoid space under the rostal basal forebrain increased slow-wave sleep up to the maximum level that can be attained physiologically. This PGD_2-sensitive, sleep-promoting zone spreads beneath the horizontal limb of the diagonal band and even towards rostral under the basal forebrain. Thus, the site of action was confined in the ventral region of the rostral basal forebrain. Our group also demonstrated that the brain type PGD synthase, which is the major enzyme responsible for the synthesis of PGD_2 in the brain, is crucial for the maintenance of physiological sleep : i.e., administration of inhibitors of this enzyme caused total insomnia. By use of in situ hybridization and immunohistochemical staining, it was shown that this enzyme is mainly located in the choroid plexus, leptomeninges, and, in less degree, the white matter. It was also demonstrated that the cerebrospinal fluid (CSF) exhibited PGD synthase activity with a highest specific activity among various brain tissues examined. The second most abundant protein in the CSF,which was known as beta-trace, was shown to be identical to the PGD synthase itself. Based on the results of this reserach, it is hypothesized that PGD_2 synthesized in the surface layr of the brain acts as a sleep promoter at the ventral surface zone of the rostral basal forebrain, and that the PGD_2 and PGD synthase (or beta-trace) in the CSF also play important roles in the sleep-wake regulation.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Yoshihiro Urade: "Structural and functional significance of cysteine residues of glutathione-independent prostaglandin D synthase." J Biol Chem. 270. 1422-1428 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Osamu Hayashi: "Tryptophan,oxygen,and sleep." Annu Rev Biochem. 63. 1-24 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hitoshi Matsumura: "Prostaglandin D_2-sensitive, sleep-promoting zone defined in the ventral surface of the rostral basal forebrain." Proc Natl Acad Sci USA. 91. 11998-12002 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kikuko Watanabe: "Identification of β-trace as prostaglandin D synthase." Biochem Biophys Res Commun. 203. 1110-1116 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shinsuke Satoh: "Promotion of sleep by prostaglandin D_2 in rats made insomniac by pretreatment with para-chlorophenylalanine." Neurosci Res. 21. 41-50 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshihiro Urade: "Dominant expression of mRNA for prostaglandin D synthase in leptomeninges,choroid plexus,and oligodendrocytes of the adult rat brain." Proc Natl Acad Sci USA. 90. 9070-9074 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshihiro Urade, Toshiki Nakata, Naomi Eguchi, Minami Kikuchi, Hiromi Kimura, Hiroyuki Toh, Osamu Hayaishi: "Structural and functional significance of cysteine residues of glutathione-independent prostaglandin D synthase." J Biol Chem. 270. 1422-1428 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Osamu Hayaishi: "Tryptophan, oxygen, and sleep" Annu Rev Biochem. 63. 1-24 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hitoshi Matsumura, Tomoko Nakajima, Toshimasa Osaka, Shinsuke Satoh, Kumiko Kawase, Etsuko Kubo, Sachi Sri Kantha, Keiko Kasahara, Osamu Hayaishi: "Prostaglandin D_2-sensitive, sleep-promoting zone defined in the ventral surface of the rostral basal forebrain." Proc Natl Acad Sci USA. 91. 11998-12002 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kikuko Watanabe, Yoshihiro Urade, Michael Mader, Charles Murphy, Osamu Hayaishi: "Identification of beta-trace as prostaglandin D synthase." Biochem Biophys Res Commun. 203. 1110-1116 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shinsuke Satoh, Hitoshi Matsumura, Tomoko Nakajima, Hirotaka Onoe, Kazuya Sakai, Teruo Nakajima, Michel Jouvet, Osamu Hayaishi: "Promotion of sleep by prostaglandin D_2 in rats made insomniac by pretreatment with para-chlorophenylalanine." Neurosci Res. 21. 41-50 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshihiro Urade, Kunio Kitahama, Hitoshi Ohishi, Takeshi Kaneko, Noboru Mizuno, Osamu Hayaishi: "Dominant expression of mRNA for prostaglandin D synthase in leptomeninges, choroid plexus, and oligodendrocytes of the adult rat brain." Proc Natl Acad Sci USA. 90. 9070-9074 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Toshimasa Osaka, Hitoshi Matsumura: "Noradrenegic inputs to sleep-related neurons in the preoptic area from the locus coeruleus and the ventrolateral medulla in the rat." Neurosci Res. 19. 39-50 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] S.Sri Kantha, H.Matsumura, E.Kubo, K.Kawase, R.Takahata, C.N.Serhan, O.Hayaishi: "Effects of prostaglandin D_2, lipoxins and leukotrienes on sleep and brain temperature of rats." Prostaglandins Leukotriences and Essential Fatty Acids. 51. 87-93 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hitoshi Matsumura: "Prostaglandin D_2-sensitive,sleep-promoting zone defined in the ventral surface of the rostral basal forebrain" Proc.Natl.Acad.Sci.USA. 91. 11998-12002 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Toshimasa Osaka: "Noradrenergic inpurts to sleep-related neurons in the preoptic area from the locus coeruleus and the ventrolateral medulla in the rat" Neuroscience Research. 19. 39-50 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shinsuke Satoh: "Promotion of sleep by prostaglandin D_2 in rats made insomniac by pretreatment with para-chlorophenylalanine" Neuroscience Research. 21. 41-50 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kikuko Watanabe: "Identification of β-trace as prostaglandin D-synthase" Biochem.Biophys.Res.Commun.203. 1110-1116 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshihiro Urade: "Structural and Functional Significance of Cysteine Residues of Glutathione-independent Prostaglandin D Synthase" Journal of Biological Chemistry. 270. 1422-1428 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshihiro Urade: "Recent advances in research on prostaglandin D,E,and F synthases" J.Lipid Mediators. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hayashi,O.: "Prostaglandins D_2 and E_2 are endogenous sleep regulating substances in the brain" Sleep Res.(Abstracts). 22. 479-479 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Matsumura.H.: "Site of action for the sleep‐promoting effect of prostaglandin D_2: examination in freely‐behaving rats bilateral administration using microdialysis techenique." Jpn.J.Psychiatr.Neurol.(Proceeding). (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Urade.Y.: "Dominant expression of mRNA for prostaglandin D synthase in leptomeninges,choroid plexus,and oligodendrocytes of the adult rat brain." Proc.Natl.Acad.Sci.USA. 90. 9070-9074 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Osaka,T.: "Noradrenergic inputs to sleep‐related neurons in the preoptic area from the locus coeruleus and the ventrolateral medulla in the rat." Neurosci.Res.(in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Takahata.R.: "Seasonal variation in levels of prostaglandins D_2,E_2 and F_<2alpha> in the brain of a mammalian hibemator,the asian chipmunk." Prostaglandins Leukotrienes and Essential Fatty Acids. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Kantha,S,S.: "Effects of prostaglandin D_2,lipoxins and leukotrienes on sleep and brain temperature of rats." Prostaglandins Leukotrienes and Essential Fatty Acids. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Matsumura,H.: "Inhibition of sleep in rats by inorganic selenium compounds,inhibitors of prostaglandin D synthase." Proc.Natl.Acad.Sci.USA. 88. 9046-9050 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hayaishi,O.: "Molecular mechanisms of sleep-wake regulation:roles of prostaglandins D_2 and E_2." FASEB J.5. 2575-2581 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nagata,A.: "Human brain prostaglandin D synthase has been evolutionarily differentiated from Iipophilicligand carrier proteins." Proc.Natl.Acad.Sci.USA. 88. 4020-4024 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hayaishi,O.: "Molecular mechanisms of sleep regulation by prostaglandin D_2." AUS-SLEEP '92 International Update Conference Fifth Annual Meeting of the Australasian Sleep Association,Abstracts. 118-118 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Matsumura,H.: "The effects of lovastatin,simvastatin and pravastatin on sleep-wake activity in rats." XI International Symposium on Drugs Affecting Lipid Metabolism,Abstracts. 76-76 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 鈴木 登志子: "ウシ胸腺プロスタグランジンE合成酵素" 第65回日本生化学大会発表抄録集. 1043-1043 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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